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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05667493




Registration number
NCT05667493
Ethics application status
Date submitted
12/07/2022
Date registered
28/12/2022
Date last updated
28/03/2024

Titles & IDs
Public title
An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
Scientific title
An Open-Label Extension Study to Assess the Long-Term Safety of Eplontersen (ION-682884) in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
Secondary ID [1] 0 0
2022-000826-74
Secondary ID [2] 0 0
ION-682884-CS12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eplontersen

Experimental: Eplontersen - Eplontersen will be administered once every month by sub-cutaneous (SC) injection for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first.


Treatment: Drugs: Eplontersen
Eplontersen will be administered by SC injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Timepoint [1] 0 0
Baseline up to 36 months
Primary outcome [2] 0 0
Change From Baseline in Platelet Count
Timepoint [2] 0 0
Baseline up to 36 months
Primary outcome [3] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Timepoint [3] 0 0
Baseline up to 36 months
Primary outcome [4] 0 0
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Timepoint [4] 0 0
Baseline up to 36 months
Primary outcome [5] 0 0
Change From Baseline in AST
Timepoint [5] 0 0
Baseline up to 36 months
Primary outcome [6] 0 0
Change From Baseline in ALT
Timepoint [6] 0 0
Baseline up to 36 months
Primary outcome [7] 0 0
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
Timepoint [7] 0 0
Baseline up to 36 months
Primary outcome [8] 0 0
Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)
Timepoint [8] 0 0
Baseline up to 36 months
Primary outcome [9] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADA)
Timepoint [9] 0 0
Baseline up to 36 months
Secondary outcome [1] 0 0
Change From Baseline in Transthyretin (TTR) Serum Levels
Timepoint [1] 0 0
Baseline up to 36 months
Secondary outcome [2] 0 0
Change From Baseline in 6-minute Walk Test (6MWT)
Timepoint [2] 0 0
Baseline up to 36 months
Secondary outcome [3] 0 0
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)
Timepoint [3] 0 0
Baseline up to 36 months
Secondary outcome [4] 0 0
Change From Baseline in Short Form Health Survey Questionnaire (SF-36)
Timepoint [4] 0 0
Baseline up to 36 months
Secondary outcome [5] 0 0
Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)
Timepoint [5] 0 0
Baseline up to 36 months
Secondary outcome [6] 0 0
Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)
Timepoint [6] 0 0
Baseline up to 36 months
Secondary outcome [7] 0 0
Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)
Timepoint [7] 0 0
Baseline up to 36 months

Eligibility
Key inclusion criteria
1. Satisfactory completion of Treatment Period and the End of Treatment Visit of the
Index Study (ION-682884-CS2) OR diagnosis of ATTR-CM and satisfactory participation on
ISIS 420915- CS101 study as judged by the Investigator and Sponsor.

2. Investigator is willing to treat the participant with open-label eplontersen.

3. Willingness to adhere to vitamin A supplementation per protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Permanently discontinued study drug administration while participating in the Index
Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).

2. Have any new condition or worsening of an existing condition that in the opinion of
the Investigator or Sponsor would make the participant unsuitable for enrolment, or
which could interfere with the participant participating in or completing the study,
including the need for treatment with medications disallowed in the Index Study.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2029
Actual
Sample size
Target
1400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
West AustraliaWA
Recruitment hospital [1] 0 0
Advara HeartCare Murdoch - Murdoch
Recruitment hospital [2] 0 0
Advara HeartCare - Joondalup
Recruitment hospital [3] 0 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 0 0
6150 - Murdoch
Recruitment postcode(s) [2] 0 0
6027 - Joondalup
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Austria
State/province [24] 0 0
Graz
Country [25] 0 0
Austria
State/province [25] 0 0
Innsbruck
Country [26] 0 0
Belgium
State/province [26] 0 0
Brugge
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
France
State/province [30] 0 0
La Roche-sur-Yon
Country [31] 0 0
France
State/province [31] 0 0
Nantes
Country [32] 0 0
France
State/province [32] 0 0
Pessac
Country [33] 0 0
Germany
State/province [33] 0 0
Homburg
Country [34] 0 0
Germany
State/province [34] 0 0
Münster
Country [35] 0 0
Germany
State/province [35] 0 0
Würzburg
Country [36] 0 0
Greece
State/province [36] 0 0
Athens
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Rehovot
Country [39] 0 0
Italy
State/province [39] 0 0
Firenze
Country [40] 0 0
Italy
State/province [40] 0 0
Pavia
Country [41] 0 0
Portugal
State/province [41] 0 0
Guimarães
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Majadahonda
Country [45] 0 0
Spain
State/province [45] 0 0
Murcia
Country [46] 0 0
Sweden
State/province [46] 0 0
Göteborg
Country [47] 0 0
Sweden
State/province [47] 0 0
Skellefteå
Country [48] 0 0
United Kingdom
State/province [48] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ionis Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and tolerability of extended dosing with
eplontersen in participants with ATTR-CM.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05667493
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ionis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
(844) 520-3239
Fax 0 0
Email 0 0
ionisATTRCM2study@clinicaltrialmedia.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05667493